Chemistry - A European Journal最新文献

Selective methylation is among the most relevant transformations in synthetic chemistry and the discovery of new drug molecules. A methyl group is typically installed using strong electrophiles such as methyl iodide or dimethyl sulfate, which are associated with safety hazards and limited chemoselectivity. A promising strategy for circumventing these limitations relies on splitting the methylation into a two-step procedure under mediator control. However, such reactions, including the Mukaiyama redox condensation, currently lack applicability since the mediator is lost as organic waste, resulting in a low atom economy. We have developed a flavin-mediated methylation strategy with easily accessible methyl diphenylphosphinite (Ph₂POMe) as the source of the methyl group. The flavin mediator is easily recovered by a simple acidic treatment followed by oxidation with air. Detailed NMR spectroscopic studies and structural information by X-ray crystallography paint a clear mechanistic picture, while we show the chemoselective modification of a variety of organic substrates and also demonstrate trideuteromethylation. Methylation is accomplished with complex molecules, including venetoclax and nevirapine. We envision the flavin-mediated methodology to be adaptable to other alkylation reactions besides methylation. Within the realm of the latter, chemoselective modification of nucleobases stands out as a promising target.

Apurinic/apyrimidinic endonuclease-1 (APE1) is a repair enzyme that efficiently cleaves abasic (AP) site damage in duplex DNA. Reports of in vitro activity assays between APE1 and single-stranded G-quadruplex (ssG4) reveal significant decreases in the endonuclease activity. Here, we identify that the low yields observed represent cleavage of the noncanonical folds that did not adopt a complete G4 fold. This conclusion is supported through circular dichroism analysis and activity assays analyzing the cleavage rate, folding impact on cleavage, and product inhibition. Studies were performed on AP-containing ssG4 and duplex-embedded G4 scaffolds. The CD spectra of a non-G4 containing potential quadruplex sequence reveal a noncanonical structure. APE1 can cleave an AP in these non-G4 conformation(s) in high yields comparable to the preferred duplex substrate. There is direct evidence of decreasing APE1 activity with increasing G4 folding in ssG4 and duplex-G-quadruplex-duplex (DGD) systems. Also observed is a positional dependency on yield in the non-G4 DGD scaffolds, but not in the non-G4 ssG4 scaffolds. In conclusion, our studies provide evidence that APE1 efficiently cleaves noncanonical conformations in G4-like structures, highlighting the control of secondary structure on APE1 endonuclease activity.

Organic semiconductor electrocatalysts (OSEs), which integrate the properties of organic semiconductors with electrocatalytic performance, have emerged as promising alternatives to traditional noble metal catalysts due to their low cost, earth abundance, and design flexibility. This article reviews the unique structural features of organic material systems, including small organic molecules, conjugated polymers, covalent organic frameworks (COFs), and organic hybrid materials. It elucidates the structure-activity relationship between the features of organic catalysts and their catalytic advantages. It discusses design strategies, including molecular engineering and interface regulation. Also, it explores applications in key reactions, including the hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), carbon dioxide reduction reaction (CO₂RR), and nitrogen reduction reaction (NRR). Despite challenges in stability and large-scale preparation, OSEs show great potential in sustainable energy conversion, offering insights for advancing clean energy technologies.

Spin qubits are among the most promising candidates for quantum information processing and sensing technologies. Their potential to function even at elevated temperatures makes them particularly attractive for future devices. However, while extensive studies have been carried out on S = 1/2 systems, high-spin complexes remain much less explored as spin qubit platforms. In this study, we prepared a Zn(II)-based MOF, [CH₆N₃][Zn(HCOO)₃], doped with trace amounts of Mn(II) ions (S = 5/2, 0.2, and 0.02 mol%). Magnetic measurements under static fields revealed slow relaxation phenomena dominated by direct and Raman-like processes. Importantly, Q-band pulsed ESR confirmed quantum coherence between M_S = ±1/2 sublevels, achieving phase memory times (T₂) up to 5.4 µs at 10 K, which is significantly longer than those reported in other Mn(II)-based systems. Rabi nutation experiments verified coherent spin control and multilevel transitions, while Wigner matrix analysis revealed reorientation of the nuclear quantization axis during spin flips. Notably, coherence persisted above 150 K, attributed to the stabilization provided in the MOF's hydrogen-bonded lattice. This work represents the first demonstration of high-spin Mn(II) qubits with measurable coherence at elevated temperatures, underscoring MOFs as versatile and tunable platforms for advancing quantum materials and molecular spin-based technologies.

γ-Butenolides are widespread structural motifs found in many natural and unnatural products which display an impressive range of biological activities. Among them, ε-keto-γ-butenolides represent underestimated butenolide frameworks, which could serve as valuable platforms to build complex structures, for example, heterobicyclic derivatives. Quite unexpectedly, despite the apparent simplicity of their structures, efficient synthetic methodologies enabling the construction of chiral, ε-keto-γ-butenolide architectures are quite underdeveloped. In this context, herein we present a novel, photoinduced regio- and chemoselective γ-alkylation of 2-silyloxyfurans with 2-bromoketones providing a practical access to ε-ketobutenolide scaffolds in racemic format, in one single step and high yields. The usefulness of these products as starting materials to build chiral, fused-heterobicycle lactone derivatives was demonstrated by the implementation of a two-step strategy which successfully delivered unprecedented phenyltetrahydrofuro[3,2-b]furan-2(3H)-one and tetrahydrofuro[3,2-c]pyridazin-6(1H)-one chemotypes.

Fluorocycloparaphenylenes (F-CPPs) are strained, cyclic, π-conjugated molecules with unique electronic and supramolecular properties. Here, we report a novel synthetic approach to create F-CPPs via the formation of macrocyclic palladium complexes that contain covalent Pd-C bonds. The thermal stability of the fluorinated biaryl Pd motifs and the reversibility of the formation of Pd-C bonds enable the self-assembly of macrocyclic Pd complexes. Subsequent ligand exchange with Xantphos facilitates reductive elimination, yielding various F-CPPs that incorporate tetrafluorophenylene, phenylene, or thienylene units. A structural analysis revealed that the thienylene-based F-CPPs adopt tubular packing structures due to their high fluorine content. Optical measurements and time-dependent density-functional-theory (TD-DFT) calculations demonstrated size- and structure-dependent absorption and emission behavior. This Pd-mediated synthetic strategy provides a new platform for the synthesis of functionalized CPPs with tailored properties for potential applications in nanomaterials and supramolecular chemistry.

The Scholl reaction has long stood as a powerful tool for forging C-C bonds in polycyclic aromatic hydrocarbons (PAHs) yet controlling regioselectivity and accessing new reactivity remains a formidable challenge. Here, we unveil a strategically designed platform that exploits electronic tuning within tetraarylthiophenes (TATs) to achieve highly selective [c]-face oxidative cyclodehydrogenation, delivering phenanthro[9,10-c]thiophenes in exceptional yields, a pathway previously inaccessible. Beyond annulation, we uncover a novel oxidative ring-opening reaction, wherein these phenanthrothiophenes undergo selective C─S bond cleavage to yield 9,10-diaroylphenanthrenes-a transformation unprecedented in thiophene chemistry under Scholl-type reaction. Remarkably, we integrate both steps into a one-pot cascade protocol, streamlining direct synthesis from TATs to complex diketone architectures in notable yields. Mechanistic studies, including radical trapping and EPR spectroscopy, point out toward radical (cation/anion) pathways governing these transformations. This dual reactivity-from ring construction to ring cleavage-spotlights new horizons in Scholl chemistry, expanding synthetic access to diverse PAH frameworks and edition of functional edges, that may have potential applications as functional materials in organic electronics.

Designing and synthesizing condensed, thermally stable zeolites by inverse sigma expansion of open-framework zeolites has been well achieved. However, creating thermally stable open-framework zeolites through sigma expansion of condensed-frameworks remains rare. Herein, we present the rational design and synthesis of a thermally stable medium-pore aluminosilicate zeolite SCM-53, which possesses a 2D 10 × 10-ring channel system. The framework of SCM-53 was theoretically predicted by sigma expansion of the framework of SCM-51, a small-pore aluminosilicate zeolite featuring a 2D 8 × 8-ring channel system prepared by calcination of the layered precursor SCM-50. SCM-53 was rationally synthesized by successive interlayer silylation and calcination treatments of SCM-50. The structure of SCM-53 was validated by powder X-ray diffraction (PXRD), scanning transmission electron microscopy (STEM), nuclear magnetic resonance (NMR) spectroscopy, and N₂ absorption measurement. Our results demonstrate that SCM-53 possesses accessible micropores (5.9 × 4.9 Å), an ultrathin nanosheet morphology (∼15 nm), and high thermal stability (up to 800 °C), suggesting its potential for adsorption and catalytic applications. We anticipate that sigma expansion offers a promising approach for the rational design and synthesis of targeted novel zeolite structures.

Aerobic copper-mediated oxidative processes play a pivotal role in the context of enzymatic oxidation and catalysis. Herein, the first high-valent copper(III) trifluoromethyl hydroxide with the tetrameric heterocubane structure [Cu(CF₃)₂(OH)]₄ was synthesized by air oxidation of copper(I) in the presence of TMSCF₃/KF and fully characterized, including X-ray crystallography. This unique compound displays versatile reactivity, functioning as a hydroxide base in neutralization reactions with acids, which affords a broad variety of high-valent Cu(III) complexes with two trifluoromethyl groups. The synthetic relevance of copper(III) trifluoromethyl hydroxide for boronic acid trifluoromethylation was demonstrated. The natural population analysis (NPA) charge distribution in the tetrameric heterocubane was studied by DFT calculations, which support the experimentally observed behavior of this compound as a weak hydroxide base, and revealed the positive NPA charge of +1.157 on high-valent copper.

In contrast to the previously reported TiCl₄-catalyzed [2+2] synthesis of 2-azetines using internal alkynes and ethyl 3,3,3-trifluoro-2-((methylsulfonyl)imino)propanoate [CF₃C(═NMs)CO₂Et], electron-abundant terminal alkynes do not necessarily require a catalyst for the [2+2] cycloaddition process. In this study, we demonstrate that the 2-azetines, which were produced by using 2-ethynyl-N,N-dialkylanilines (ArC≡CH, Ar = 2-R₂NC₆H₄, R = alkyl), showed blue fluorescence (Φ = 4∼9%). The structural elucidation, using X-ray crystallographic analysis and density functional theory (DFT) calculations, of the fluorescent 2-azetines involved the pyramidalized flanking amino groups, as steric congestion prevented conventional π-conjugation between the amino and phenylene units. It is noteworthy that the C═C unit in the 2-azetine cycle plays a crucial role in the fluorescent character, and saturation of the double bond afforded the nonfluorescent azetidine derivative. Thus, the combination of the electron-donating pyramidal amino group and the electron-accepting π-molecular skeleton, including the appropriate bridging aryl spacer, is a promising molecular design for developing unique photo-functional N-heterocyclic materials. In addition, to investigate the o-aminophenyl effect on the 2-azetine framework, we employed the azole-substituted phenylacetylenes for the [2+2] cycloaddition. 2-(N-Pyrrolyl) and 2-(N-indolyl)phenylacetylenes facilitated the [2+2] cycloaddition process predominantly and afforded the corresponding 2-azetines exclusively, whereas the [2+2] synthesis reported so far included the byproducts.